The natural history of great toe amputations

The purpose of this study is to report the prevalence of reamputation following resection of the great toe and first ray in adults with diabetes. We abstracted the medical records of 90 diabetic great-toe and first-ray amputees admitted between 1981 and 1991. The most common etiologies of initial amputations were ulcer with soft tissue infection (39%), ulcer with osteomyelitis (32%), and puncture wounds (12%). Sixty percent of all patients had a second amputation, 21% had a third, and 7% had a fourth. Fifteen percent of the patients who had a second amputation had it contralaterally. Seventeen percent subsequently underwent a below-knee amputation and 11% had a Transmetatarsal amputation on the same extremity, 3% had a below-knee amputation, and 2% a transmetatarsal amputation contralaterally. The mean time from the first to the second amputation was approximately 10 months. The results of this study suggest that a large proportion of patients undergoing an amputation at the level of the great toe or first ray have subsequent amputations in the first year following the initial procedure. Additionally, it appears that the contralateral foot may be at significant risk for distal amputation following resection of the hallux or first day.     

CATH--a hierarchic classification of protein domain structures

BACKGROUND: Protein evolution gives rise to families of structurally related proteins, within which sequence identities can be extremely low. As a result, structure-based classifications can be effective at identifying unanticipated relationships in known structures and in optimal cases function can also be assigned. The ever increasing number of known protein structures is too large to classify all proteins manually, therefore, automatic methods are needed for fast evaluation of protein structures. RESULTS: We present a semi-automatic procedure for deriving a novel hierarchical classification of protein domain structures (CATH). The four main levels of our classification are protein class (C), architecture (A), topology (T) and homologous superfamily (H). Class is the simplest level, and it essentially describes the secondary structure composition of each domain. In contrast, architecture summarises the shape revealed by the orientations of the secondary structure units, such as barrels and sandwiches. At the topology level, sequential connectivity is considered, such that members of the same architecture might have quite different topologies. When structures belonging to the same T-level have suitably high similarities combined with similar functions, the proteins are assumed to be evolutionarily related and put into the same homologous superfamily. CONCLUSIONS: Analysis of the structural families generated by CATH reveals the prominent features of protein structure space. We find that nearly a third of the homologous superfamilies (H-levels) belong to ten major T-levels, which we call superfolds, and furthermore that nearly two-thirds of these H-levels cluster into nine simple architectures. A database of well-characterised protein structure families, such as CATH, will facilitate the assignment of structure-function/evolution relationships to both known and newly determined protein structures.     

Evaluation of Hopscotch Method for Transient Ground-Water Flow

The hopscotch finite-difference technique is shown to be a fast and accurate way to simulate transient, saturated, ground-water flow in relatively typical but heterogeneous 2D and 3D domains. The odd-even hopscotch (OEH) and line hopscotch methods are reviewed, and their implementation for saturated ground-water flow is presented. The OEH scheme, which is a second-order accurate explicit process, is efficient, requiring only six floating point operations per mesh node and time step, and is unconditionally stable (for saturated ground-water flow). Numerical experiments on typical 2D meshes (2,500 nodes) with synthetic, randomly heterogeneous hydraulic conductivity, suggest that the OEH process is approximately 1.5 times faster than the alternating direction implicit method and 3–4 times faster than the Crank-Nicolson implicit method using preconditioned conjugate gradient iteration. Similar experiments on medium-sized 3D meshes (87,500 nodes) suggest that the OEH process is between 7 and 10 times faster than the Crank-Nicolson preconditioned conjugate gradient method. Although the numerical results presented illustrate only typical test problem performance, they nevertheless clearly indicate promise for using OEH to simulate transient ground-water flow in 2D and, especially, 3D heterogeneous domains requiring fine spatial meshes.     

Circulating angiotensin II and renal sodium handling in man: a dose-response study

1. Animal studies have shown that angiotensin II has a biphasic effect on urinary sodium excretion. To examine whether this is also true in man, we studied seven salt-replete male subjects in a single-blind placebo-controlled manner. 2. While undergoing maximum diuresis, subjects were infused with 0, 1, 2, 5 or 10 ng of angiotensin II min-1 kg-1 over 80 min. Subjects were studied while seated, and stood every 20 min for urine collection. 3. Angiotensin II produced a dose-dependent antidiuretic effect. The urine flow rate, in ml/min expressed as the change from baseline with increasing dose of angiotensin, was: +3.4 +/- 1.77, -1.26 +/- 0.49 (P < 0.05), -2.75 +/- 1.23 (P < 0.05), -4.21 +/- 0.82 (P < 0.05) and -6.51 +/- 1.07 (P < 0.01). 4. In contrast, the effect of angiotensin II on sodium excretion showed a flat dose-response curve beyond 5 ng min-1 kg-1. The urinary sodium excretion, in mumol/min expressed as the change from baseline with increasing dose of angiotensin, was: 9.5 +/- 21.2, -18.9 +/- 29.6, -37.0 +/- 11.6 (P < 0.05), -67.7 +/- 19.6 (P < 0.01) and -63.8 +/- 14.3 (P < 0.01). 5. The fractional distal reabsorption of sodium, determined by using the lithium clearance technique, showed a rise with all doses of angiotensin II used and reached statistical significance with the top two doses. 6. Unlike antidiuresis, antinatriuresis after graded doses of angiotensin II in human subjects showed a flat dose-response curve beyond 5 ng min-1 kg-1. Pressor doses of angiotensin II also have a significant effect on the distal tubule in promoting sodium reabsorption.